This proposal is in two parts and continues our previous work. Part I involves full-temperature (4.2-300K) magnetochemical studies by Faraday and SQUID methodologies of various derivatives of fully-oxidized (resting) cytochrome c oxidase for the purpose of determining the nature and magnitude (plus/minus J value) of the ferro- or antiferromagnetic exchange interaction between (Fe(III) and Cu(II) at the binuclear (Cyt.a3-3+(bridge)Cuu2+) active site. Oxidases from both mammalian (bovine) and bacterial (T. thermophilus) sources will be studied. The new derivatives of the enzyme proposed for our continuing studies are the resting (anaerobically prepared), resting.F-, resting.H202 and "pulsed" derivatives of bovine oxidase and the resting and resting.CN- forms of the T. thermophilus enzyme. Magnetochemical results for these additional derivatives, along with our previous findings for the resting, resting.CN-, and resting.HCO2- derivatives of bovine oxidase will lend further insight into the leading candidates for the catalytically-involved, bridged active site structure: (1) a Mu-oxo case with (Cyt.a3-3+-0-Cuu2+), (2) a Mu-mercapto case with (Cyt.a3-3+-S-Cuu2+), and to a lesser extent, a Mu-imidazolato case with (Cyt.a3-3+(imid)Cuu2+). Part II will involve the synthesis, structural characterization (x-ray crystallography and EXAFS) and study (magnetochemistry, RR, epr, and Mossbauer spectroscopy) of various [(TPP)FeIII(bridge)CuII] model compounds (or useful synthetic analogues) where the bridges are the oxidase possibilities: oxo, mercapto, imidazolato, CN-, HCO2-, F-, and H202. Through preliminary and on-going work, twenty of these novel heterobimetallic species are already in hand and are yielding information pertaining to the oxidase active site structure and thereby the mechanism whereby the 02 + 4H+ + 4e- produces 2H20 enzyme reaction is catalyzed.